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A single-parasite transcriptional atlas of Toxoplasma Gondii reveals novel control of antigen expression.

Yuan Xue | Terence C Theisen | Suchita Rastogi | Abel Ferrel | Stephen R Quake | John C Boothroyd
eLife | 2020

Toxoplasma gondii, a protozoan parasite, undergoes a complex and poorly understood developmental process that is critical for establishing a chronic infection in its intermediate hosts. Here, we applied single-cell RNA-sequencing (scRNA-seq) on >5,400 Toxoplasma in both tachyzoite and bradyzoite stages using three widely studied strains to construct a comprehensive atlas of cell-cycle and asexual development, revealing hidden states and transcriptional factors associated with each developmental stage. Analysis of SAG1-related sequence (SRS) antigenic repertoire reveals a highly heterogeneous, sporadic expression pattern unexplained by measurement noise, cell cycle, or asexual development. Furthermore, we identified AP2IX-1 as a transcription factor that controls the switching from the ubiquitous SAG1 to rare surface antigens not previously observed in tachyzoites. In addition, comparative analysis between Toxoplasma and Plasmodium scRNA-seq results reveals concerted expression of gene sets, despite fundamental differences in cell division. Lastly, we built an interactive data-browser for visualization of our atlas resource.

Pubmed ID: 32065584

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R01 AI129529
  • Agency: NIH HHS, United States
    Id: 5T32AI007328-30
  • Agency: NIH HHS, United States
    Id: RO1 AI29529
  • Agency: NIAID NIH HHS, United States
    Id: F30 AI124589
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI021423

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BD FACSDiva Software (tool)

RRID:SCR_001456

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RRID:SCR_001628

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RRID:SCR_002474

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RRID:SCR_008539

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RRID:SCR_013331

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